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P05126

- KPCB_BOVIN

UniProt

P05126 - KPCB_BOVIN

Protein

Protein kinase C beta type

Gene

PRKCB

Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 152 (01 Oct 2014)
      Sequence version 4 (18 May 2010)
      Previous versions | rss
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    Functioni

    Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. May participate in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Binds 3 calcium ions per subunit. The ions are bound to the C2 domain By similarity.By similarity

    Enzyme regulationi

    Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-500 (activation loop of the kinase domain), Thr-642 (turn motif) and Ser-661 (hydrophobic region), need to be phosphorylated for its full activation. Specifically inhibited by enzastaurin (LY317615) By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi186 – 1861Calcium 1; via carbonyl oxygenBy similarity
    Metal bindingi187 – 1871Calcium 1By similarity
    Metal bindingi187 – 1871Calcium 2By similarity
    Metal bindingi193 – 1931Calcium 2By similarity
    Metal bindingi246 – 2461Calcium 1By similarity
    Metal bindingi246 – 2461Calcium 2By similarity
    Metal bindingi247 – 2471Calcium 2; via carbonyl oxygenBy similarity
    Metal bindingi248 – 2481Calcium 1By similarity
    Metal bindingi248 – 2481Calcium 2By similarity
    Metal bindingi248 – 2481Calcium 3By similarity
    Metal bindingi251 – 2511Calcium 3By similarity
    Metal bindingi252 – 2521Calcium 3; via carbonyl oxygenBy similarity
    Metal bindingi254 – 2541Calcium 1By similarity
    Metal bindingi254 – 2541Calcium 3By similarity
    Binding sitei371 – 3711ATPPROSITE-ProRule annotation
    Active sitei466 – 4661Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri36 – 8651Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri101 – 15151Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd
    BLAST
    Nucleotide bindingi348 – 3569ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. androgen receptor binding Source: UniProtKB
    2. ATP binding Source: UniProtKB-KW
    3. calcium channel regulator activity Source: Ensembl
    4. chromatin binding Source: UniProtKB
    5. histone binding Source: UniProtKB
    6. histone kinase activity (H3-T6 specific) Source: UniProtKB
    7. ligand-dependent nuclear receptor transcription coactivator activity Source: UniProtKB
    8. protein kinase C activity Source: UniProtKB-EC
    9. zinc ion binding Source: InterPro

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. B cell activation Source: UniProtKB
    3. B cell receptor signaling pathway Source: UniProtKB
    4. calcium ion transport Source: Ensembl
    5. cellular calcium ion homeostasis Source: Ensembl
    6. cellular response to carbohydrate stimulus Source: Ensembl
    7. histone H3-T6 phosphorylation Source: UniProtKB
    8. intracellular signal transduction Source: InterPro
    9. negative regulation of glucose transport Source: UniProtKB
    10. negative regulation of insulin receptor signaling pathway Source: UniProtKB
    11. positive regulation of angiogenesis Source: UniProtKB
    12. positive regulation of B cell receptor signaling pathway Source: UniProtKB
    13. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
    14. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
    15. positive regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
    16. regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    17. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Chromatin regulator, Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Adaptive immunity, Apoptosis, Immunity, Transcription, Transcription regulation

    Keywords - Ligandi

    ATP-binding, Calcium, Metal-binding, Nucleotide-binding, Zinc

    Enzyme and pathway databases

    BRENDAi2.7.11.13. 908.
    ReactomeiREACT_205897. Activation of NF-kappaB in B cells.
    REACT_209033. G alpha (z) signalling events.
    REACT_212308. Response to elevated platelet cytosolic Ca2+.
    REACT_217496. Trafficking of GluR2-containing AMPA receptors.
    REACT_217562. WNT5A-dependent internalization of FZD4.
    REACT_220570. Disinhibition of SNARE formation.
    REACT_221009. Depolymerisation of the Nuclear Lamina.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein kinase C beta type (EC:2.7.11.13)
    Short name:
    PKC-B
    Short name:
    PKC-beta
    Gene namesi
    Name:PRKCB
    Synonyms:PRKCB1
    OrganismiBos taurus (Bovine)
    Taxonomic identifieri9913 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
    ProteomesiUP000009136: Chromosome 25

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity. Membrane By similarity; Peripheral membrane protein By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB
    3. plasma membrane Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 671670Protein kinase C beta typePRO_0000055683Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Modified residuei16 – 161Phosphoserine; by autocatalysisSequence Analysis
    Modified residuei17 – 171Phosphothreonine; by autocatalysisSequence Analysis
    Modified residuei250 – 2501Phosphothreonine; by autocatalysisBy similarity
    Modified residuei324 – 3241Phosphothreonine; by autocatalysisSequence Analysis
    Modified residuei500 – 5001Phosphothreonine; by PDPK1By similarity
    Modified residuei504 – 5041PhosphothreonineBy similarity
    Modified residuei635 – 6351Phosphothreonine; by autocatalysisBy similarity
    Modified residuei642 – 6421Phosphothreonine; by autocatalysisBy similarity
    Modified residuei661 – 6611Phosphoserine; by autocatalysisBy similarity
    Modified residuei662 – 6621Phosphotyrosine; by SYKBy similarity

    Post-translational modificationi

    Phosphorylation on Thr-500 within the activation loop renders it competent to autophosphorylate. Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol. Autophosphorylation on other sites i.e. in the N-terminal and hinge regions have no effect on enzyme activity. Phosphorylation at Tyr-662 by SYK induces binding with GRB2 and contributes to the activation of MAPK/ERK signaling cascade By similarity.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PRIDEiP05126.

    Interactioni

    Subunit structurei

    Interacts with PDK1. Interacts in vitro with PRKCBP1. Interacts with PHLPP1 and PHLPP2; both proteins mediate its dephosphorylation. Interacts with KDM1A/LSD1, PKN1 and ANDR By similarity.By similarity

    Protein-protein interaction databases

    BioGridi159587. 1 interaction.
    STRINGi9913.ENSBTAP00000027870.

    Structurei

    3D structure databases

    ProteinModelPortaliP05126.
    SMRiP05126. Positions 37-288, 339-668.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini173 – 26088C2PROSITE-ProRule annotationAdd
    BLAST
    Domaini342 – 600259Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini601 – 66969AGC-kinase C-terminalAdd
    BLAST

    Sequence similaritiesi

    Contains 1 AGC-kinase C-terminal domain.Curated
    Contains 1 C2 domain.PROSITE-ProRule annotation
    Contains 2 phorbol-ester/DAG-type zinc fingers.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri36 – 8651Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri101 – 15151Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00750000117339.
    HOGENOMiHOG000233022.
    HOVERGENiHBG108317.
    InParanoidiP05126.
    KOiK02677.
    OMAiQAHIDRE.
    OrthoDBiEOG77M8QM.
    TreeFamiTF351133.

    Family and domain databases

    Gene3Di2.60.40.150. 1 hit.
    InterProiIPR000961. AGC-kinase_C.
    IPR000008. C2_dom.
    IPR020454. DAG/PE-bd.
    IPR011009. Kinase-like_dom.
    IPR017892. Pkinase_C.
    IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR014375. Protein_kinase_C_a/b/g.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00130. C1_1. 2 hits.
    PF00168. C2. 1 hit.
    PF00069. Pkinase. 1 hit.
    PF00433. Pkinase_C. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000550. PKC_alpha. 1 hit.
    PRINTSiPR00360. C2DOMAIN.
    PR00008. DAGPEDOMAIN.
    SMARTiSM00109. C1. 2 hits.
    SM00239. C2. 1 hit.
    SM00133. S_TK_X. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF49562. SSF49562. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
    PS50004. C2. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    PS00479. ZF_DAG_PE_1. 2 hits.
    PS50081. ZF_DAG_PE_2. 2 hits.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform Beta-I (identifier: P05126-1) [UniParc]FASTAAdd to Basket

    Also known as: PRKCB1

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MADPAAGPPP SEGEESTVRF ARKGALRQKN VHEVKNHKFT ARFFKQPTFC    50
    SHCTDFIWGF GKQGFQCQVC CFVVHKRCHE FVTFSCPGAD KGPASDDPRS 100
    KHKFKIHTYS SPTFCDHCGS LLYGLIHQGM KCDTCMMNVH KRCVMNVPSL 150
    CGTDHTERRG RIYIQAHIER EVLIVVVRDA KNLVPMDPNG LSDPYVKLKL 200
    IPDPKSESKQ KTKTIKCSLN PEWNETFRFQ LKESDKDRRL SVEIWDWDLT 250
    SRNDFMGSLS FGISELQKAG VDGWFKLLSQ EEGEYFNVPV PPEGSEGNEE 300
    LRQKFERAKI GPGPKTPEEK TTNTISKFDN NGNRDRMKLT DFNFLMVLGK 350
    GSFGKVMLSE RKGTDELYAV KILKKDVVIQ DDDVECTMVE KRVLALPGKP 400
    PFLTQLHSCF QTMDRLYFVM EYVNGGDLMY HIQQVGRFKE PHAVFYAAEI 450
    AIGLFFLQSK GIIYRDLKLD NVMLDSEGHI KIADFGMCKE NIWDGVTTKT 500
    FCGTPDYIAP EIIAYQPYGK SVDWWAFGVL LYEMLAGQAP FEGEDEDELF 550
    QSIMEHNVAY PKSMSKEAVA ICKGLMTKHP GKRLGCGPEG ERDIKEHAFF 600
    RYIDWEKLER KEIQPPYKPK ARDKRDTSNF DKEFTRQPVE LTPTDKLFIM 650
    NLDQNEFAGF SYTNPEFVIN V 671
    Length:671
    Mass (Da):76,790
    Last modified:May 18, 2010 - v4
    Checksum:i1F31D6A9D3C4C61F
    GO
    Isoform Beta-II (identifier: P05126-2) [UniParc]FASTAAdd to Basket

    Also known as: PRKCB2

    The sequence of this isoform differs from the canonical sequence as follows:
         622-671: RDKRDTSNFD...YTNPEFVINV → CGRNAENFDR...SEFLKPEVKS

    Show »
    Length:673
    Mass (Da):76,933
    Checksum:i61711D08707B005B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti576 – 5761M → I in AAA30703. 1 PublicationCurated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei622 – 67150RDKRD…FVINV → CGRNAENFDRFFTRHPPVLT PPDQEVIRNIDQSEFEGFSF VNSEFLKPEVKS in isoform Beta-II. 1 PublicationVSP_039222Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M13974 mRNA. Translation: AAA30703.1.
    BC140620 mRNA. Translation: AAI40621.1.
    PIRiA24664. KIBOC2.
    RefSeqiNP_777012.1. NM_174587.1.
    XP_005224747.1. XM_005224690.1. [P05126-1]
    UniGeneiBt.5435.

    Genome annotation databases

    EnsembliENSBTAT00000027870; ENSBTAP00000027870; ENSBTAG00000020921. [P05126-2]
    ENSBTAT00000042942; ENSBTAP00000040548; ENSBTAG00000020921. [P05126-1]
    GeneIDi282325.
    KEGGibta:282325.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M13974 mRNA. Translation: AAA30703.1 .
    BC140620 mRNA. Translation: AAI40621.1 .
    PIRi A24664. KIBOC2.
    RefSeqi NP_777012.1. NM_174587.1.
    XP_005224747.1. XM_005224690.1. [P05126-1 ]
    UniGenei Bt.5435.

    3D structure databases

    ProteinModelPortali P05126.
    SMRi P05126. Positions 37-288, 339-668.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 159587. 1 interaction.
    STRINGi 9913.ENSBTAP00000027870.

    Proteomic databases

    PRIDEi P05126.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSBTAT00000027870 ; ENSBTAP00000027870 ; ENSBTAG00000020921 . [P05126-2 ]
    ENSBTAT00000042942 ; ENSBTAP00000040548 ; ENSBTAG00000020921 . [P05126-1 ]
    GeneIDi 282325.
    KEGGi bta:282325.

    Organism-specific databases

    CTDi 5579.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00750000117339.
    HOGENOMi HOG000233022.
    HOVERGENi HBG108317.
    InParanoidi P05126.
    KOi K02677.
    OMAi QAHIDRE.
    OrthoDBi EOG77M8QM.
    TreeFami TF351133.

    Enzyme and pathway databases

    BRENDAi 2.7.11.13. 908.
    Reactomei REACT_205897. Activation of NF-kappaB in B cells.
    REACT_209033. G alpha (z) signalling events.
    REACT_212308. Response to elevated platelet cytosolic Ca2+.
    REACT_217496. Trafficking of GluR2-containing AMPA receptors.
    REACT_217562. WNT5A-dependent internalization of FZD4.
    REACT_220570. Disinhibition of SNARE formation.
    REACT_221009. Depolymerisation of the Nuclear Lamina.

    Miscellaneous databases

    NextBioi 20806122.

    Family and domain databases

    Gene3Di 2.60.40.150. 1 hit.
    InterProi IPR000961. AGC-kinase_C.
    IPR000008. C2_dom.
    IPR020454. DAG/PE-bd.
    IPR011009. Kinase-like_dom.
    IPR017892. Pkinase_C.
    IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR014375. Protein_kinase_C_a/b/g.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00130. C1_1. 2 hits.
    PF00168. C2. 1 hit.
    PF00069. Pkinase. 1 hit.
    PF00433. Pkinase_C. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000550. PKC_alpha. 1 hit.
    PRINTSi PR00360. C2DOMAIN.
    PR00008. DAGPEDOMAIN.
    SMARTi SM00109. C1. 2 hits.
    SM00239. C2. 1 hit.
    SM00133. S_TK_X. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49562. SSF49562. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS51285. AGC_KINASE_CTER. 1 hit.
    PS50004. C2. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    PS00479. ZF_DAG_PE_1. 2 hits.
    PS50081. ZF_DAG_PE_2. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Multiple, distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways."
      Coussens L., Parker P.J., Rhee L., Yang-Feng T.L., Chen E., Waterfield M.D., Francke U., Ullrich A.
      Science 233:859-866(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-II).
    2. NIH - Mammalian Gene Collection (MGC) project
      Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA-I).
      Strain: Hereford.
      Tissue: Fetal pons.
    3. "The molecular heterogeneity of protein kinase C and its implications for cellular regulation."
      Nishizuka Y.
      Nature 334:661-665(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.

    Entry informationi

    Entry nameiKPCB_BOVIN
    AccessioniPrimary (citable) accession number: P05126
    Secondary accession number(s): A5D7N0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 13, 1987
    Last sequence update: May 18, 2010
    Last modified: October 1, 2014
    This is version 152 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3